Taurine prevents cardiomyocyte death by inhibiting NADPH oxidase-mediated calpain activation.
Taurine has been shown to prevent cardiomyocyte apoptosis. This study investigated the effects of taurine on NADPH oxidase and calpain activation in mediating apoptosis in cardiomyocytes. Apoptosis was induced by norepinephrine (NE) in cultured adult rat ventricular cardiomyocytes. NE (5 microM) increased NADPH oxidase activation and reactive oxygen species (ROS) production and induced apoptosis. These effects of NE on cardiomyocytes were diminished by taurine (0.5 mg/kg) but not beta-alanine. Inhibition of gp91(phox)-NADPH oxidase or ROS production protected cardiomyocytes from apoptosis. NE also induced calpain-1 activation in cardiomyocytes. This effect of NE on calpain was abrogated by gp91(phox)-NADPH oxidase inhibition or ROS scavengers and was mimicked by H(2)O(2) (25 microM) in cardiomyocytes. Pharmacological inhibitors of calpain or overexpression of calpastatin, a specific calpain inhibitor, blocked calpain activation and prevented cardiomyocyte apoptosis during NE stimulation. Furthermore, taurine treatment inhibited NE- or H(2)O(2)-induced calpain activation in cardiomyocytes. In conclusion, NADPH oxidase induces calpain activation, leading to apoptosis in NE-induced cardiomyocytes. Taurine inhibits NADPH oxidase and calpain activation. Thus, inhibition of NADPH oxidase-mediated calpain activation may be an important mechanism for taurine's antiapoptotic action in cardiomyocytes.
Li
Ying
Y
Lawson Health Research Institute, Department of Medicine, University of Western Ontario, London, Canada.
Arnold
J Malcolm O
JM
Pampillo
Macarena
M
Babwah
Andy V
AV
Peng
Tianqing
T
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006352:Heart Ventricles / Q000166:cytology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000378:metabolism* / Q000494:pharmacology; D019076:Transgenes
D002135:Calcium-Binding Proteins; D013654:Taurine; C033668:calpastatin; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D002154:Calpain; D009638:Norepinephrine